Recombinant canstatin inhibits angiopoietin‐1‐induced angiogenesis and lymphangiogenesis

Jeon, Hoon; Yoo, Ki Hyun; Park, Jong-Hwa; Jeong, Han‐Sin; Chung, In Sik

doi:10.1002/ijc.26353

Cited by 42 publications

(37 citation statements)

References 26 publications

(25 reference statements)

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“…Arresten inhibits EC migration and tumor growth through the engagement of integrin α 1 β 1 and inhibition of MAP kinase [65,71]. Similarly, canstatin also inhibits EC migration and tube formation [72] and impairs angiopoietin-1-induced angiogenesis and lymphangiogenesis [73]. The mechanisms of action involve the binding to integrins α ν β 3 and α ν β 5 , and inhibition of Protein Kinase B (PKB) also known as Akt focal adhesion kinase (FAK) and mammalian Target of Rapamycin (mTOR) [74].…”

Section: Collagens: a Major Source Of Anti-angiogenic Fragmentsmentioning

confidence: 99%

Extracellular Matrix, a Hard Player in Angiogenesis

Mongiat

Andreuzzi

Tarticchio

et al. 2016

IJMS

164

137

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The extracellular matrix (ECM) is a complex network of proteins, glycoproteins, proteoglycans, and polysaccharides. Through multiple interactions with each other and the cell surface receptors, not only the ECM determines the physical and mechanical properties of the tissues, but also profoundly influences cell behavior and many physiological and pathological processes. One of the functions that have been extensively explored is its impingement on angiogenesis. The strong impact of the ECM in this context is both direct and indirect by virtue of its ability to interact and/or store several growth factors and cytokines. The aim of this review is to provide some examples of the complex molecular mechanisms that are elicited by these molecules in promoting or weakening the angiogenic processes. The scenario is intricate, since matrix remodeling often generates fragments displaying opposite effects compared to those exerted by the whole molecules. Thus, the balance will tilt towards angiogenesis or angiostasis depending on the relative expression of pro- or anti-angiogenetic molecules/fragments composing the matrix of a given tissue. One of the vital aspects of this field of research is that, for its endogenous nature, the ECM can be viewed as a reservoir to draw from for the development of new more efficacious therapies to treat angiogenesis-dependent pathologies.

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Section: Collagens: a Major Source Of Anti-angiogenic Fragmentsmentioning

confidence: 99%

Extracellular Matrix, a Hard Player in Angiogenesis

Mongiat

Andreuzzi

Tarticchio

et al. 2016

IJMS

164

137

View full text Add to dashboard Cite

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“…In line with the previous observation of mouse models showing a clear difference of angiogenesis morphology in BM of different primaries, our data could classify patients with identical diagnosis in similar clusters based on their angiogenic gene expression signature. Genes with known involvement in angiogenic processes including VEGFA [7], CEACAM1 [30], PECAM1 [31], CXCL12 (also known as SDF1-α) [32], KIT [33], TNF [34], and collagens [35,36] were at least 10 times upregulated in all groups indicating the necessity of those factors for the establishment of the basic characteristics of the angiogenesis process. These genes are mainly involved in proliferation of endothelial cells and activation of growth factors [30,31,33].…”

Section: Discussionmentioning

confidence: 93%

Expression profiling of angiogenesis-related genes in brain metastases of lung cancer and melanoma

et al. 2015

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Brain metastases (BM) are the most common brain tumors of adults and are associated with fatal prognosis. Formation of new blood vessels, named angiogenesis, was proposed to be the main hallmark of the growth of BM. Previous preclinical evidence revealed that angiogenic blockage might be considered for treatment; however, there were varying responses. In this study, we aimed to characterize the expression pattern of angiogenesis-related genes in BM of lung cancer and melanoma, which might be of importance for the different responses against anti-angiogenic treatment. Fifteen snap-frozen tissues obtained from BM of non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and melanoma patients were analyzed for angiogenesis-related genes using a commercially available gene expression kit. Epilepsy tissue was used as control. Expression values were analyzed using hierarchical clustering investigating relative fold changes and mapping to Omicsnet protein interaction network. CXCL10, CEACAM1, PECAM1, KIT, COL4A2, COL1A1, and HSPG2 genes were more than 50-fold up-regulated in all diagnosis groups when compared to control, whereas genes such as ANGPT4, PDGFRB, and SERPINF1 were down-regulated only in SCLC and melanoma groups, respectively. Using hierarchical clustering, 12 out of 15 cases were allocated to the correct histological primary tumor type. We identified genes with consistent up-regulation in BM of lung cancer and melanoma and other genes with differential expression across BM of these tumor types. Our data may be of relevance for targeted therapy or prophylaxis of BM using anti-angiogenic agents.

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“…Recombinant canstatin alone dose‐dependently inhibited the proliferation of LECs . To evaluate the antilymphangiogenic effects of recombinant canstatin, concentrations of 0.5 and 40 μ g/mL were used for mild and moderate levels of cell proliferation inhibition . Both tube formation and migration induced by VEGF‐A in HLMECs were inhibited by recombinant canstatin, even under conditions that did not induce the death of HLMECs (Fig.…”

Section: Discussionmentioning

confidence: 99%

Recombinant canstatin inhibits VEGF‐A‐induced lymphangiogenesis and metastasis in an oral squamous cell carcinoma SCC‐VII animal model

et al. 2016

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We describe the inhibitory effects of recombinant canstatin on tumor growth and lymphangiogenesis induced by an oral squamous cell carcinoma (SCC) using an orthotropic oral SCC animal model. Recombinant canstatin treatment decreased final tumor volumes and weights, as well as densities of blood and lymphatic vessels. Lung metastasis of oral SCC was significantly reduced in recombinant canstatin‐treated animals. Recombinant canstatin reduced vascular endothelial growth factor (VEGF)‐A expression in SCC‐VII cells treated with the hypoxia mimetic agent, CoCl2. VEGF‐A induced in vivo lymphatic vessel formation in a Matrigel plug, but this was remarkably reduced in a recombinant canstatin‐treated Matrigel. Recombinant canstatin suppressed the expression of vascular endothelial growth factor receptors (VEGFR)‐1 and ‐2 stimulated by VEGF‐A. Based on immunohistochemical analysis, recombinant canstatin significantly reduced the expression of VEGF‐A, VEGFR‐1, and ‐2 in SCC‐VII‐induced tumors. Recombinant canstatin did not affect the expression of VEGF‐C or VEGFR‐3. In addition, recombinant canstatin suppressed the VEGF‐A‐induced phosphorylation of VEGFR‐1 and ‐2. Our results indicate that recombinant canstatin exhibits antitumoral and antilymphangiogenic activities against oral SCC cells. Antilymphangiogenic signaling by recombinant canstatin is probably mediated by the suppression of the integrin αvβ3/VEGFR‐1 and/or ‐2 signaling induced by VEGF‐A. Our results also suggest that recombinant canstatin has a high potential to inhibit oral SCC‐induced tumors and lymphatic metastasis.

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Recombinant canstatin inhibits angiopoietin‐1‐induced angiogenesis and lymphangiogenesis

Cited by 42 publications

References 26 publications

Extracellular Matrix, a Hard Player in Angiogenesis

Extracellular Matrix, a Hard Player in Angiogenesis

Expression profiling of angiogenesis-related genes in brain metastases of lung cancer and melanoma

Recombinant canstatin inhibits VEGF‐A‐induced lymphangiogenesis and metastasis in an oral squamous cell carcinoma SCC‐VII animal model

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